NLRP3 inflammasome as a sensor of micro- and nanoplastics immunotoxicity

Alijagić, Andi; Hedbrant, Alexander; Persson, Annina H.; Larsson, Maria; Engwall, Magnus; Särndahl, Eva

doi:10.3389/fimmu.2023.1178434

Cited by 17 publications

(2 citation statements)

References 111 publications

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“…The top cytokine USR by z score for +MP vs. PBS was IL-1β, a cytokine matured and released via inflammasome activation ( Figure 1 ). Our observation thus support a recent speculation that MPs might activate the inflammasome ( 144 ), with IL-1β also a dominant signature at 6 dpi for BA.5+MP vs. BA.5.…”

Section: Discussionsupporting

confidence: 91%

Microplastics dysregulate innate immunity in the SARS-CoV-2 infected lung

Bishop,

Yan,

Nguyen

et al. 2024

Front. Immunol.

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IntroductionGlobal microplastic (MP) pollution is now well recognized, with humans and animals consuming and inhaling MPs on a daily basis, with a growing body of concern surrounding the potential impacts on human health.MethodsUsing a mouse model of mild COVID-19, we describe herein the effects of azide-free 1 μm polystyrene MP beads, co-delivered into lungs with a SARS-CoV-2 omicron BA.5 inoculum. The effect of MPs on the host response to SARS-CoV-2 infection was analysed using histopathology and RNA-Seq at 2 and 6 days post-infection (dpi).ResultsAlthough infection reduced clearance of MPs from the lung, virus titres and viral RNA levels were not significantly affected by MPs, and overt MP-associated clinical or histopathological changes were not observed. However, RNA-Seq of infected lungs revealed that MP exposure suppressed innate immune responses at 2 dpi and increased pro-inflammatory signatures at 6 dpi. The cytokine profile at 6 dpi showed a significant correlation with the ‘cytokine release syndrome’ signature observed in some COVID-19 patients.DiscussionThe findings are consistent with the recent finding that MPs can inhibit phagocytosis of apoptotic cells via binding of Tim4. They also add to a growing body of literature suggesting that MPs can dysregulate inflammatory processes in specific disease settings.

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Section: Discussionsupporting

confidence: 91%

Microplastics dysregulate innate immunity in the SARS-CoV-2 infected lung

Bishop,

Yan,

Nguyen

et al. 2024

Front. Immunol.

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“…Exposure of cells to particles of various materials can lead to the formation of reactive oxygen species in mitochondria or phagosomes ( 49 , 59 ). Further, the release of cathepsin B can trigger ROS accumulation within the cell ( 58 ).…”

Section: Discussionmentioning

confidence: 99%

Influence of metallic particles and TNF on the transcriptional regulation of NLRP3 inflammasome-associated genes in human osteoblasts

Sellin,

Hansmann,

Bader

et al. 2024

Front. Immunol.

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IntroductionThe release of mature interleukin (IL-) 1β from osteoblasts in response to danger signals is tightly regulated by the nucleotide-binding oligomerization domain leucine-rich repeat and pyrin-containing protein 3 (NLRP3) inflammasome. These danger signals include wear products resulting from aseptic loosening of joint arthroplasty. However, inflammasome activation requires two different signals: a nuclear factor-kappa B (NF-κB)-activating priming signal and an actual inflammasome-activating signal. Since human osteoblasts react to wear particles via Toll-like receptors (TLR), particles may represent an inflammasome activator that can induce both signals.MethodsTemporal gene expression profiles of TLRs and associated intracellular signaling pathways were determined to investigate the period when human osteoblasts take up metallic wear particles after initial contact and initiate a molecular response. For this purpose, human osteoblasts were treated with metallic particles derived from cobalt-chromium alloy (CoCr), lipopolysaccharides (LPS), and tumor necrosis factor-alpha (TNF) alone or in combination for incubation times ranging from one hour to three days. Shortly after adding the particles, their uptake was observed by the change in cell morphology and spectral data.ResultsExposure of osteoblasts to particles alone increased NLRP3 inflammasome-associated genes. The response was not significantly enhanced when cells were treated with CoCr + LPS or CoCr + TNF, whereas inflammation markers were induced. Despite an increase in genes related to the NLRP3 inflammasome, the release of IL-1β was unaffected after contact with CoCr particles.DiscussionAlthough CoCr particles affect the expression of NLRP3 inflammasome-associated genes, a single stimulus was not sufficient to prime and activate the inflammasome. TNF was able to prime the NLRP3 inflammasome of human osteoblasts.

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